1. Field of the Invention
The present invention relates to apparatus for small particle treatment of the respiratory tract including the lungs.
2. Prior Art
As a result of suggestions made by one of the inventors, in consultations at Ft. Detrick, Md., scientists at the U.S. Army Medical Research Institute of Infectious Diseases in 1975 adapted a Collison nebulizer to deliver a continuous flow of small particle aerosols to mice infected with influenza virus. This system was described by Young and his associates in 1977 (Young, H. W., Dominik, J. W., Walker, J. S., Larson, E. W. Continuous aerosol therapy system using a modified Collison nebulizer. J Clin Microb 1977; 5(2):131-136). Several papers were published subsequently dealing with the use of this technology to treat influenza infections in mice with rimantadine (Stephen, E. L., Dominik, J. W., Moe, J. B., Spertzel, R. O., Walker, J. S. Treatment of influenza infection of mice by using rimantadine hydrochloride by the aerosol and intraperitoneal routes. Antimicrob Ag Chemother 1975; 8(2):154-158, amantadine and ribavirin Walker, J. S., Stephen, E. L., Spertzel, R. O. Small particle aerosols of antiviral compounds in treatment of type A influenza pneumonia in mice. J Infect Dis 1976; 133:A140-A144). Another study compared the effect of ribavirin given by the intraperitoneal and aerosol routes in influenza infections in mice (Stephen, E. L., Dominik, J. W., Moe, J. B., Walker, J. S. Therapeutic effects of ribavirin given by the intraperitoneal or aerosol route against influenza virus infections in mice. Antimicrob Ag Chemother 1976; 10(3):549-554) and on the physiological alterations in mice with influenza, untreated and treated with ribavirin aerosol (Arensman, J. B., Dominik, J. W., Hilmas, D. E. Effects of small particle aerosols of rimantadine and ribavirin on arterial blood pH and gas tensions and lung water content of A2 influenza-infected mice. Antimicrob Ag Chemother 1977; 12(1):40-46). Berendt and associates made further studies of treatment of influenza in mice with ribavirin aerosol (Berendt, R. F., Walker, J. S., Dominik, J. W., Stephen, E. L. Response of influenza virus-infected mice to selected doses of ribavirin administered intraperitoneally or by aerosol. Antimicrob Ag Chemother 1977; 11(6):1069-1070).
Based on the foregoing work, technology was adapted for human use by the inventor in his laboratory (Wilson, S. Z., Knight, V., Moore, R., and Larson, E. W. Amantadine small particle aerosol: generation and delivery to man. Proc Sol Exper Biol Med 1979; 161:350-354). Studies in mice in the inventor's laboratory confirmed the earlier results and, in addition, showed that a substantial therapeutic effect was demonstrable when treatment was delayed for as long as five days after inoculation (Knight, V., Wilson, S. Z., Wyde, P. R., Drake, S., Couch, R. B., Galegov, G. A., Novokhatsky, A. S. Small particle aerosols of amantadine and ribavirin in the treatment of influenza. In Ribavirin: A Broad Spectrum Antiviral Agent. Smith, R. A. and Kirkpatrick, W. (ed), Academic Press, Inc., New York 1980; pp. 129-145; Wilson, S. Z., Knight, V., Wyde, P. R., Drake, S., Couch, R. B. Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice. Antimicrob Ag Chemother 1980; 17(4):642-648; Knight, V., Bloom, K., Wilson, S. Z., Wilson, R. K. Amantadine aerosol in humans. Antimicrob Ag Chemother 1979; 16(4):572-578). These studies additionally show that a combination of ribavirin and amantadine increase the effectiveness of therapy.
While the animal studies, in this case mice, demonstrated the efficacy of aerosol treatment, and encouraged human trial, the human trials were done with the realization that therapeutic effect, tolerance and toxicity may be quite different in man and animals. For example, in Wilson, et al, 1979, Amantadine Small Particle Aerosol: Generation and Delivery to Man, supra, in using the arbitrary criteria for retention of aerosol in mice and man, the estimated dosages in mice were approximate four-fold those in man when similar exposure periods were employed. Up until the present development, there was no determination made of the aerosol concentration of the drug which provided an effective, tolerant and nontoxic concentration for man. In addition, most available nebulizers provide coarse particles, that is particles having a mean diameter of 10 microns and over which are too coarse to penetrate effectively into the lungs.
While the small particle or nebulizer apparatus described and used in Wilson, et al, 1979, generated small particles and produced the results there set forth, it had the following disadvantages, (1) the valve from the bag to the mask would clog with precipitated drugs from the aerosol and the mere insertion of mechanical valves, however efficient, inevitably creates some obstruction that in some degree obstructs the flow of aerosol to the patient; (2) the air exhaled by the patient is forced into the aerosol stream flowing to the patient and the patient then inhales his own exhaled air from which the drug had been removed; and (3) the efficiency of the apparatus needed to be improved to provide a higher concentration of drug per liter of aerosol.
U.S. Pat. No. 4,211,711 is directed to ribavirin, and the small particle aerosol or nebulizer apparatus of this invention is particularly well suited to deliver small particle ribavirin for treatment of the respiratory tract including the lungs.
The most pertinent prior art relating to the present invention known to the applicant is the prior art set forth above in this section of the Background of the Invention.